ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1702G>A (p.Gly568Ser) (rs140464432)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119225 SCV000153969 uncertain significance Multiple endocrine neoplasia, type 2 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 568 of the RET protein (p.Gly568Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs140464432, ExAC 0.02%). This variant has not been reported in the literature in individuals with RET-related disease. ClinVar contains an entry for this variant (Variation ID: 132762). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000355156 SCV000339854 uncertain significance not provided 2016-03-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564831 SCV000674795 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Counsyl RCV000662493 SCV000785005 uncertain significance Multiple endocrine neoplasia, type 2a 2017-03-14 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764897 SCV000896057 uncertain significance Congenital central hypoventilation; Hirschsprung disease 1; Multiple endocrine neoplasia, type 2b; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia, type 2a 2018-10-31 criteria provided, single submitter clinical testing

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